ABSTRACT: MOOD, MOTHER AND CHILD: THE PSYCHOBIOLOGY OF DYADIC RESILIENCE Perinatal depression (PND) affects more than 400,000 mother-infant dyads in the US each year, with devastating consequences. Mothers with PND exhibit reduced sensitivity to infant needs, increasing infant risk for impaired emotional regulation and insecure attachment. These dysregulated interactions in the first year of life are associated with impaired cognitive and socioemotional development, including child psychopathology and impaired executive function (EF). Mothers who experience PND are more likely to have continuing or relapsing depression and anxiety disorders, conferring further risk. Nevertheless, despite exposure to PND, some dyads emerge intact. The long-term goal of this research is to identify the psychobiological underpinnings of resilience among mother-child dyads exposed to PND and longer-term maternal depression and anxiety trajectories (MDATs). The objectives of this proposal are to characterize MDAT heterogeneity during the first 5 years of the child?s life, to identify mediators that explain the mechanisms through which MDATs influence child outcomes, and identify moderators that may serve as intervention points for promoting dyadic resilience. We will leverage an existing pool of participants in the Mood, Mother and Infant (MMI) study (R01HD073220, mmi.web.unc.edu, PI Stuebe), an ongoing longitudinal cohort study that we have led of mother-infant dyads (N=222) who have been extensively phenotyped during the first postpartum year. Our central hypothesis is that oxytocin plays a central role in dyadic development, indexed by associations between OT psychobiology, genetics and epigenetics and both MDATs and child development outcome. The rationale for this work is that our findings will inform targeted interventions to facilitate resilience and diminish the sequelae of maternal depression. We will accomplish the objective of our application by pursuing the following specific aims via an MMI follow-up study, the Mood, Mother and Child (MMC) study: 1) Elucidate the role of OT in the maternal psychobiological underpinnings of MDATs and parenting behavior, including effects of exogenous oxytocin (OT) on HPA axis reactivity; 2) Determine psychosocial mediators and moderators of associations between MDATs and child developmental outcome; and 3) Determine the extent to which child OXT and OXTR genotype moderates associations between MDATs, sensitivity, attachment quality, and developmental outcome; quantify the extent to which child epigenetic changes in OT and OXTR mediate associations between MDATs and developmental outcome. The expected outcomes of this work will be the determination of both predictive and protective factors for mother-infant dyads affected by depression and anxiety, laying the groundwork for novel approaches to promote resilience. Such results will have a positive impact by informing interventions to prevent intergenerational transmission of depression and anxiety.